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Q9UBB5 (MBD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methyl-CpG-binding domain protein 2
Alternative name(s):
Demethylase
Short name=DMTase
Methyl-CpG-binding protein MBD2
Gene names
Name:MBD2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length411 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases. Acts as transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.12 Ref.14 Ref.20

Subunit structure

Heterodimer with MBD3. Component of the MeCP1 complex that contains HDAC1 and HDAC2. Binds DNMT1, MIZF, GPN1, SIN3A, GATAD2A/p66-alpha and GATAD2B/p66-beta. Interacts with DHX9. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.21

Subcellular location

Nucleus. Note: Nuclear, in discrete foci. Detected at replication foci in late S phase. Ref.1 Ref.10

Tissue specificity

Highly expressed in brain, heart, kidney, stomach, testis and placenta. Ref.4

Sequence similarities

Contains 1 MBD (methyl-CpG-binding) domain.

Caution

Functional studies (Ref.4, Ref.7 and Ref.12) have used a C-terminal fragment of isoform 1 which has been described originally as isoform MBD2b(Ref.1) but cannot however be proven by supporting cDNA sequences.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   LigandDNA-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular protein complex assembly

Inferred from electronic annotation. Source: Ensembl

maternal behavior

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Non-traceable author statement Ref.2. Source: UniProtKB

positive regulation of Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

heterochromatin

Inferred from electronic annotation. Source: Ensembl

histone deacetylase complex

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.9. Source: UniProtKB

   Molecular_functionC2H2 zinc finger domain binding

Inferred from physical interaction Ref.9. Source: UniProtKB

chromatin binding

Inferred from electronic annotation. Source: Ensembl

mRNA binding

Inferred from electronic annotation. Source: Ensembl

methyl-CpG binding

Inferred from direct assay PubMed 21029866Ref.20. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction PubMed 11984006. Source: UniProtKB

satellite DNA binding

Traceable author statement Ref.1. Source: ProtInc

siRNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UBB5-1)

Also known as: MBD2a; MBD2b;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 3 (identifier: Q9UBB5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     235-302: GKPDLNTTLP...SDVTEQIIKT → LRWNTHRPAP...YSRQNQSFPP
     303-411: Missing.
Note: Incomplete sequence.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 411411Methyl-CpG-binding domain protein 2
PRO_0000096260

Regions

Domain145 – 21369MBD
Region1 – 149149Necessary for interaction with DHX9
Compositional bias6 – 140135Gly-rich
Compositional bias50 – 9647Arg-rich

Amino acid modifications

Modified residue1811Phosphoserine Ref.15 Ref.18
Modified residue4071Phosphoserine Ref.13 Ref.15 Ref.17 Ref.18

Natural variations

Alternative sequence235 – 30268GKPDL…QIIKT → LRWNTHRPAPWHALSRLCLL IRCLLCLECAYPLPLHLVNS YSSKTQLHCLHLWEACPAYS RQNQSFPP in isoform 3.
VSP_011077
Alternative sequence303 – 411109Missing in isoform 3.
VSP_011078

Secondary structure

.... 411
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (MBD2a) (MBD2b) [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: FC4E5E0CF9BA0FFA

FASTA41143,255
        10         20         30         40         50         60 
MRAHPGGGRC CPEQEEGESA AGGSGAGGDS AIEQGGQGSA LAPSPVSGVR REGARGGGRG 

        70         80         90        100        110        120 
RGRWKQAGRG GGVCGRGRGR GRGRGRGRGR GRGRGRPPSG GSGLGGDGGG CGGGGSGGGG 

       130        140        150        160        170        180 
APRREPVPFP SGSAGPGPRG PRATESGKRM DCPALPPGWK KEEVIRKSGL SAGKSDVYYF 

       190        200        210        220        230        240 
SPSGKKFRSK PQLARYLGNT VDLSSFDFRT GKMMPSKLQK NKQRLRNDPL NQNKGKPDLN 

       250        260        270        280        290        300 
TTLPIRQTAS IFKQPVTKVT NHPSNKVKSD PQRMNEQPRQ LFWEKRLQGL SASDVTEQII 

       310        320        330        340        350        360 
KTMELPKGLQ GVGPGSNDET LLSAVASALH TSSAPITGQV SAAVEKNPAV WLNTSQPLCK 

       370        380        390        400        410 
AFIVTDEDIR KQEERVQQVR KKLEEALMAD ILSRAADTEE MDIEMDSGDE A 

« Hide

Isoform 3 [UniParc].

Checksum: CCEC65D926222717
Show »

FASTA30231,745

References

« Hide 'large scale' references
[1]"Identification and characterization of a family of mammalian methyl-CpG binding proteins."
Hendrich B., Bird A.
Mol. Cell. Biol. 18:6538-6547(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 157-411 (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION.
Tissue: Testis.
[2]"Genomic structure and chromosomal mapping of the murine and human mbd1, mbd2, mbd3, and mbd4 genes."
Hendrich B., Abbott C., McQueen H., Chambers D., Cross S.H., Bird A.
Mamm. Genome 10:906-912(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lymph.
[4]"A mammalian protein with specific demethylase activity for mCpG DNA."
Bhattacharya S.K., Ramchandani S., Cervoni N., Szyf M.
Nature 397:579-583(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION (ISOFORM 1), TISSUE SPECIFICITY.
[5]"MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex."
Ng H.-H., Zhang Y., Hendrich B., Johnson C.A., Turner B.M., Erdjument-Bromage H., Tempst P., Reinberg D., Bird A.
Nat. Genet. 23:58-61(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH MECP1 AND HDAC1.
[6]"MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase."
Tatematsu K., Yamazaki T., Ishikawa F.
Genes Cells 5:677-688(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, HETERODIMERIZATION WITH MBD3, INTERACTION WITH DNMT1.
[7]"The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding domain and binds directly to Sin3A."
Boeke J., Ammerpohl O., Kegel S., Moehren U., Renkawitz R.
J. Biol. Chem. 275:34963-34967(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION (ISOFORM 1), INTERACTION WITH SIN3A.
[8]"Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1."
Humphrey G.W., Wang Y., Russanova V.R., Hirai T., Qin J., Nakatani Y., Howard B.H.
J. Biol. Chem. 276:6817-6824(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC1, IDENTIFICATION BY MASS SPECTROMETRY.
[9]"Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2."
Sekimata M., Takahashi A., Murakami-Sekimata A., Homma Y.
J. Biol. Chem. 276:42632-42638(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MIZF.
[10]"Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3."
Brackertz M., Boeke J., Zhang R., Renkawitz R.
J. Biol. Chem. 277:40958-40966(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH P66ALPHA AND P66BETA, SUBCELLULAR LOCATION.
[11]"MBDin, a novel MBD2-interacting protein, relieves MBD2 repression potential and reactivates transcription from methylated promoters."
Lembo F., Pero R., Angrisano T., Vitiello C., Iuliano R., Bruni C.B., Chiariotti L.
Mol. Cell. Biol. 23:1656-1665(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GPN1.
[12]"Antithetic effects of MBD2a on gene regulation."
Fujita H., Fujii R., Aratani S., Amano T., Fukamizu A., Nakajima T.
Mol. Cell. Biol. 23:2645-2657(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DHX9.
[13]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction."
Brackertz M., Gong Z., Leers J., Renkawitz R.
Nucleic Acids Res. 34:397-406(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GATAD2A AND GATAD2B.
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-407, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[18]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181 AND SER-407, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Probing the dynamic distribution of bound states for methylcytosine-binding domains on DNA."
Cramer J.M., Scarsdale J.N., Walavalkar N.M., Buchwald W.A., Ginder G.D., Williams D.C. Jr.
J. Biol. Chem. 289:1294-1302(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING.
[21]"p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex."
Gnanapragasam M.N., Scarsdale J.N., Amaya M.L., Webb H.D., Desai M.A., Walavalkar N.M., Wang S.Z., Zu Zhu S., Ginder G.D., Williams D.C. Jr.
Proc. Natl. Acad. Sci. U.S.A. 108:7487-7492(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 360-393 IN COMPLEX WITH GATAD2A, SUBUNIT, INTERACTION WITH GATAD2A.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF072242 mRNA. Translation: AAC68871.1.
AF072246 mRNA. Translation: AAC68875.1.
AF120989, AF120988 Genomic DNA. Translation: AAD56596.1.
AF120993 expand/collapse EMBL AC list , AF120988, AF120989, AF120990, AF120991, AF120992 Genomic DNA. Translation: AAD56597.1.
BC032638 mRNA. Translation: AAH32638.1.
RefSeqNP_003918.1. NM_003927.4.
NP_056647.1. NM_015832.4.
UniGeneHs.25674.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L2LNMR-B360-393[»]
ProteinModelPortalQ9UBB5.
SMRQ9UBB5. Positions 149-213, 360-393.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114445. 33 interactions.
IntActQ9UBB5. 5 interactions.
MINTMINT-210249.
STRING9606.ENSP00000256429.

Chemistry

DrugBankDB01355. Hexobarbital.

PTM databases

PhosphoSiteQ9UBB5.

Polymorphism databases

DMDM50401198.

Proteomic databases

PaxDbQ9UBB5.
PRIDEQ9UBB5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256429; ENSP00000256429; ENSG00000134046. [Q9UBB5-1]
ENST00000583046; ENSP00000464554; ENSG00000134046. [Q9UBB5-3]
GeneID8932.
KEGGhsa:8932.
UCSCuc002lfg.2. human. [Q9UBB5-1]
uc002lfh.2. human. [Q9UBB5-3]

Organism-specific databases

CTD8932.
GeneCardsGC18M051615.
HGNCHGNC:6917. MBD2.
HPACAB037282.
MIM603547. gene.
neXtProtNX_Q9UBB5.
PharmGKBPA30660.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG316386.
HOGENOMHOG000013073.
HOVERGENHBG052417.
InParanoidQ9UBB5.
KOK11590.
OMANCISICC.
OrthoDBEOG7QNVMV.
PhylomeDBQ9UBB5.
TreeFamTF325032.

Gene expression databases

ArrayExpressQ9UBB5.
BgeeQ9UBB5.
CleanExHS_MBD2.
GenevestigatorQ9UBB5.

Family and domain databases

Gene3D3.30.890.10. 2 hits.
InterProIPR016177. DNA-bd_dom.
IPR025884. MeCpG-bd_2/3_C_dom.
IPR001739. Methyl_CpG_DNA-bd.
[Graphical view]
PfamPF01429. MBD. 1 hit.
PF14048. MBD_C. 1 hit.
[Graphical view]
SMARTSM00391. MBD. 1 hit.
[Graphical view]
SUPFAMSSF54171. SSF54171. 1 hit.
PROSITEPS50982. MBD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMBD2. human.
GeneWikiMethyl-CpG-binding_domain_protein_2.
GenomeRNAi8932.
NextBio33582.
PROQ9UBB5.
SOURCESearch...

Entry information

Entry nameMBD2_HUMAN
AccessionPrimary (citable) accession number: Q9UBB5
Secondary accession number(s): O95242, Q9UIS8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM